A Composite Low-Grade Inflammation Score and Cancer Outcomes: Results from the Moli-sani Study

BACKGROUND: Epidemiological evidence links low-grade inflammation to an increased risk of chronic degenerative diseases, but its relationship with cancer remains controversial. This study aimed to investigate the association between a composite low-grade inflammation score and different cancer outcomes on a large epidemiological scale. METHODS: A prospective analysis was conducted among 18,933 individuals (51.8% women; age ≥35 years), free from cancer, chronic inflammation or hematological diseases, from the Moli-sani cohort. Low-grade inflammation was assessed using the INFLA-score, derived from C-reactive protein, granulocyte-to-lymphocyte ratio, leukocyte and platelet counts. Hazard ratios (HR) and 95% confidence intervals (CI) for cancer mortality, cancer-related hospitalization and colorectal cancer (CRC) were estimated across INFLA-score fifths using multivariable Cox proportional hazard models. RESULTS: During a 13.1-year follow-up, 612 cancer deaths, 1,854 cancer-related hospitalizations and 287 CRC were ascertained. Individuals in the highest INFLA-score fifth showed higher hazard of cancer mortality (HRQ5vsQ1-Q4: 1.19; 95%CI: 0.99-1.44), cancer-related hospitalization (1.21; 1.08-1.34) and CRC (1.68; 1.30-2.18), compared with lowest fifths, independently of health-related behaviors and chronic diseases. Associations were more pronounced for cancer mortality and hospitalization in older individuals and those with a cancer family history, and for CRC among women (all P for interaction >0.05). Increased cancer mortality hazard was observed among normal-weight and overweight individuals, but not in obese (P for interaction =0.039). CONCLUSIONS: Higher INFLA-score is associated with increased hazard of cancer hospitalization and CRC. IMPACT: Subclinical inflammation may be a prognostic indicator for cancer, underscoring the potential role of lifestyle interventions and systemic inflammation monitoring in cancer prevention.